title: The relationship between the success rate of empirical antifungal therapy with intravenous itraconazole and clinical parameters, including plasma levels of itraconazole, in immunocompromised patients receiving itraconazole oral solution as prophylaxis: a multicenter, prospective, open-label, observational study in Korea.
abstract: To identify the role of therapeutic drug monitoring of itraconazole (ITZ) in the setting of empirical antifungal therapy with intravenous (IV) ITZ, we performed a multicenter, prospective study in patients with hematological malignancies who had received antifungal prophylaxis with ITZ oral solution (OS). We evaluated the plasma levels of ITZ and hydroxy (OH) ITZ both before initiation of IV ITZ and on days 5-7 of IV ITZ. A total of 181 patients showed an overall success rate of 68.0 %. Prolonged baseline neutropenia and accompanying cardiovascular comorbidity were significantly associated with poor outcomes of the empirical antifungal therapy (P = 0.005 and P = 0.001, respectively). A significantly higher trough plasma level of OH ITZ per body weight was found in the patients who achieved success with empirical antifungal therapy (P = 0.036). There were no significant correlations between plasma concentrations of ITZ/OH ITZ (baseline or trough levels) and toxicities. Seven patients had a discontinuation of ITZ therapy due to toxicity. This study demonstrated that IV ITZ as empirical antifungal therapy was effective and therapeutic drug monitoring was helpful to estimate the outcome of empirical antifungal therapy in patients receiving antifungal prophylaxis with ITZ OS. To predict the outcome of empirical antifungal therapy with IV ITZ, we should evaluate baseline clinical characteristics and also perform the therapeutic drug monitoring of both ITZ and OH ITZ.
authors.affiliation: Division of Hematology, Department of Internal Medicine, Yonsei University College of Medicine, Severance Hospital, 50 Yonsei-ro, Seodaemun-gu, Seoul, 120-752, South Korea.
authors.forename: Jin Seok
authors.initials: JS
authors.lastname: Kim
authors.forename: June-Won
authors.initials: JW
authors.lastname: Cheong
authors.forename: Yeo-Kyeoung
authors.initials: YK
authors.lastname: Kim
authors.forename: Jinny
authors.initials: J
authors.lastname: Park
authors.forename: Yeung-Chul
authors.initials: YC
authors.lastname: Mun
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Kang
authors.forename: Hyeon Gyu
authors.initials: HG
authors.lastname: Yi
authors.forename: Je-Hwan
authors.initials: JH
authors.lastname: Lee
authors.forename: Yang Soo
authors.initials: YS
authors.lastname: Kim
authors.forename: Hun-Mo
authors.initials: HM
authors.lastname: Ryoo
authors.forename: Sung-Hyun
authors.initials: SH
authors.lastname: Kim
authors.forename: Ho Young
authors.initials: HY
authors.lastname: Kim
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Kim
authors.forename: Dong-Gun
authors.initials: DG
authors.lastname: Lee
authors.forename: Hoon-Gu
authors.initials: HG
authors.lastname: Kim
authors.forename: Hawk
authors.initials: H
authors.lastname: Kim
authors.forename: Young-Don
authors.initials: YD
authors.lastname: Joo
authors.forename: Yoo Hong
authors.initials: YH
authors.lastname: Min
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D064146:Chemotherapy-Induced Febrile Neutropenia / Q000150:complications; D016903:Drug Monitoring; D005260:Female; D019337:Hematologic Neoplasms / Q000150:complications; D006801:Humans; D017964:Itraconazole / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000097:blood / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009181:Mycoses / Q000188:drug therapy* / Q000209:etiology / Q000517:prevention & control; D011446:Prospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; C084794:hydroxyitraconazole; D017964:Itraconazole